Distinct patterns of glia repair and remyelination in antibody-mediated demyelination models of multiple sclerosis and neuromyelitis optica
Abstract
Multiple sclerosis (MS) and neuromyelitis optica (NMO) are inflammatory demyelinating disorders of the central nervous system with evidence of antibody-mediated pathology. Using ex vivo organotypic mouse cerebellar slice cultures, we have demonstrated that recombinant antibodies (rAbs) cloned from cerebrospinal fluid plasmablasts of MS and NMO patients target myelin- and astrocyte-specific antigens to induce disease-specific oligodendrocyte loss and myelin degradation. In this study, we examined glial cell responses and myelin integrity during recovery from disease-specific antibody-mediated injury. Following exposure to MS rAb and human complement (HC) in cerebellar explants, myelinating oligodendrocytes repopulated the demyelinated tissue and formed new myelin sheaths along axons. Remyelination was accompanied by pronounced microglial activation. In contrast, following treatment with NMO rAb and HC, there was rapid regeneration of astrocytes and pre-myelinating oligodendrocytes but little formation of myelin sheaths on preserved axons. Deficient remyelination was associated with progressive axonal loss and the return of microglia to a resting state. Our results indicate that antibody-mediated demyelination in MS and NMO show ...Continue Reading
References
Fingolimod (FTY720) enhances remyelination following demyelination of organotypic cerebellar slices.
Citations
New ex vivo demyelination/remyelination models to defeat multiple sclerosis and neuromyelitis optica
MOG autoantibodies trigger a tightly-controlled FcR and BTK-driven microglia proliferative response.
Related Concepts
Related Feeds
Astrocytes
Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.
Astrocytes in Repair & Regeneration
Astrocytes are glial cells found within the CNS and are able to regenerate new neurons. They become activated during CNS injury and disease. The activation leads to the transcription of new genes and the repair and regeneration of neurons. Discover the latest research on astrocytes in repair and regeneration here.
CSF & Lymphatic System
This feed focuses on Cerebral Spinal Fluid (CSF) and the lymphatic system. Discover the latest papers using imaging techniques to track CSF outflow into the lymphatic system in animal models.
B cell Differentiation
Depending on the signal received through the B cell receptor and other receptors, B cells differentiate into follicular or marginal zone B cells. Here is the latest research pertaining to this differentiation process.